Trial reportInvestigative ophthalmology & visual science2020
A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.
Trial report in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma.Nature communications · 2025Pooled it
- Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension.Translational vision science & technology · 2022Trial
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- Targeting CD148 for Antithrombotic Therapy: Functional and Molecular Evaluation of AKB-9778.Pharmacology research & perspectives · 2026Article
- Article
- FYN regulates aqueous humor outflow and IOP through the phosphorylation of VE-CADHERIN.Nature communications · 2025Article
- A Scoping Review of Rho Kinase Inhibitors and their Role in Glaucoma Treatment.Current medicinal chemistry · 2025Article
- Shikonin as a therapeutic agent in renal cell carcinoma: insights from TEK-related causal association with glaucoma.Frontiers in pharmacology · 2025Article
- VE-PTP controls a fluid shear stress set point that governs cell morphological responses through Tie-2.Frontiers in cell and developmental biology · 2025Article
- Article
- Diabetes Mellitus: A Risk Factor in Schlemm's Canal-Based Minimally Invasive Glaucoma Surgery.Journal of clinical medicine · 2024Article
- Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice.Experimental eye research · 2024Article
- Poly-Dha Sequences asJACS Au · 2024Article
- Insights to Ang/Tie signaling pathway: another rosy dawn for treating retinal and choroidal vascular diseases.Journal of translational medicine · 2024Review
- The Impact of Aging on Ocular Diseases: Unveiling Complex Interactions.Aging and disease · 2024Review
- Ubiquitination of VE-cadherin regulates inflammation-induced vascular permeability in vivo.EMBO reports · 2024Article
- Penile cavernous sinusoids are Prox1-positive hybrid vessels.Vascular biology (Bristol, England) · 2024Article
- Differential roles of FOXC2 in the trabecular meshwork and Schlemm's canal in glaucomatous pathology.Life science alliance · 2023Article
- Elevated Intraocular Pressure and Glaucomatous Optic Neuropathy: Genes to Disease Mechanisms, Therapeutic Drugs, and Gene Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Purpose: Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) activation in Schlemm's canal (SC) endothelium is required for the maintenance of IOP, making the angiopoietin/Tie2 pathway a target for new and potentially disease modifying glaucoma therapies. The goal of the present study was to examine the effects of a Tie2 activator, AKB-9778, on IOP and outflow function. Methods: AKB-9778 effects on IOP was evaluated in humans, rabbits, and mice. Localization studies of vascular endothelial protein tyrosine phosphatase (VE-PTP), the target of AKB-9778 and a negative regulator of Tie2, were performed in human and mouse eyes. Mechanistic studies were carried out in mice, monitoring AKB-9778 effects on outflow facility, Tie2 phosphorylation, and filtration area of SC. Results: AKB-9778 lowered IOP in patients treated subcutaneously for diabetic eye disease. In addition to efficacious, dose-dependent IOP lowering in rabbit eyes, topical ocular AKB-9778 increased Tie2 activation in SC endothelium, reduced IOP, and increased outflow facility in mouse eyes. VE-PTP was localized to SC endothelial cells in human and mouse eyes. Mechanistically, AKB-9778 increased the filtration area of SC for aqueous humor efflux in both wild type and in Tie2+/- mice. Conclusions: This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.